Recently, highly biocompatible polymers have been formulated to provide implantable medical devices with coatings. These coatings not only increase an implant's tissue compatibility but can also function as bioactive agent reservoirs. However, designing polymer coatings for medical devices has proven problematic. Medical device coatings must be non-toxic, durable and adhere well to device surfaces. Additionally, when the medical device comes into intimate contact with tissues such as blood and internal organs it must also be biocompatible. Furthermore, if the medical device is designed to be pliable either in operation or deployment, the coating must resist cracking, fracture and delamination.
Moreover, polymer coatings on medical devices intended to act as bioactive agent (drug) eluting devices must not only be biocompatible, structurally stable, resistant to delamination, but also chemically compatible with the drug to be administered. Furthermore, if the coating is also intended to control the drug's release rate into adjacent tissue the polymer used must possess other highly specialized properties as well such as, but not limited to appropriate glass transition temperatures and appropriate hydrophilicity/hydrophobicity indexes.
One of the most widely used techniques to modify the properties of a polymer material is to blend different polymers or copolymers together into a single mixture. The resulting polymer mixtures possess a combination of properties of each polymer or copolymer component of the blend. Not all polymers, however, are miscible and thus instead of forming a uniform blend, the polymers can form immiscible mixtures subject to phase separation and delamination. When used as coatings for medical devices this problem becomes even more pronounced. One polymer component may have a stronger affinity for the medical device surface than another and thus may layer closer to the medical device surface. The polymer component having less affinity and avidity for the medical device surface migrates away from the medical device surface resulting in a bi-layer where each polymer component retains its individual properties and the coating no longer functions as a cohesive uniform substance. When bioactive agents are included in the mixture, the problems associated with immiscibility are magnified by the addition of yet a third chemical species having unique chemical properties. An additional variable is introduced by the material of the medical device substrate.
Thus, prior art methods used to develop polymer coatings, specifically drug-eluting coatings, have been largely by trial and error. Recently, the present inventors have developed methods for reducing uncertainty in coating design by matching polymer components with bioactive agents based, in part, on solubility factors.
Thus, there is a need for improved polymeric materials suitable for coating implantable medical devices. Therefore, it is an object of the present invention to provide compositions and associated methods for a wide range of biocompatible terpolymers, useful for coating implantable medical devices.